Hybrids of coumarin–indole: design, synthesis and biological evaluation in Triton WR-1339 and high-fat diet induced hyperlipidemic rat models
| Autor: | Mohammad Imran Siddiqi, Vikash Kumar, Hardik Chandasana, Pragati Kushwaha, Manish Kumar Suthar, Jitendra Kumar Saxena, Ram K. Modukuri, Ravi Sonkar, Rabi Sankar Bhatta, Yashpal S. Chhonker, K. Bhaskara Rao, Gitika Bhatia, A.K. Khanna, Koneni V. Sashidhara |
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| Rok vydání: | 2016 |
| Předmět: |
Pharmacology
Indole test chemistry.chemical_classification 010405 organic chemistry Organic Chemistry Pharmaceutical Science Reductase Coumarin 01 natural sciences Biochemistry 0104 chemical sciences 010404 medicinal & biomolecular chemistry chemistry.chemical_compound Enzyme chemistry Mechanism of action Pharmacokinetics Oral administration Drug Discovery Hypolipidemic Agents medicine Molecular Medicine medicine.symptom |
| Zdroj: | MedChemComm. 7:1858-1869 |
| ISSN: | 2040-2511 2040-2503 |
| Popis: | In this study, a series of coumarin–indole hybrids have been synthesized and evaluated for their lipid lowering activity. Preliminary biological screening of the synthesized compounds was undertaken in an in vitro model of the HMG-CoA reductase enzyme, and the activity was confirmed in Triton WR-1339 induced hyperlipidemic rats. Among the hybrids, compound 26 was found to be the best as it significantly reduced the serum and hepatic lipid profiles in an HFD-fed hyperlipidemic rat model. The mechanism of action seems to be associated with the regulation of HMG-CoA reductase activity in the liver, which is in good agreement with binding mode studies. Compound 26 exhibited favorable pharmacokinetic behavior for its oral administration, which underscores the potential of this template as a new class of hypolipidemic agents. |
| Databáze: | OpenAIRE |
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